IgG4-related disease in Italy: clinical features and outcomes of a large cohort of patients.

OBJECTIVES: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. METHOD: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as 'definite' or 'possible' according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). RESULTS: Forty-one patients (15 females, 26 males) were included in this study: 26 with 'definite' IgG4-RD and 15 with 'possible' IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24-51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. CONCLUSIONS: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.

Cardiovascular manifestations of Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare inflammatory disorder of unknown etiology, characterised by diffuse organ infiltration of CD68-positive, CD1a-negative, S100-low/negative foamy histiocytes. It is a non-Langerhans cell histiocytosis which invariably involves bones (96% of cases). Extraskeletal involvement is observed in about 50% of cases. Cardiovascular involvement affects more than 20% of patients and associates with poor prognosis, conferring a reduced response to treatment. Frequent findings are pericardial effusion (24% of patients), "coated aorta", a perivascular circumferential thickening of the aorta, and pericardial thickening. Other typical features include right atrial mass with pseudo-tumoural appearance and histiocytes' infiltration of right atrial walls, atrioventricular sulcus and interatrial septum. After the recent introduction of cardiac cine MRI in the clinical assessment of patients affected by ECD, a growing body of case reports and retrospective data showed that cardiovascular involvement is present more frequently than previously thought and that it is relatively often asymptomatic. Hence, clinicians should systematically screen ECD patients for occult cardiovascular involvement by means of highly sensitive imaging tools. Despite these recent novelties, comprehensive literature reviews focusing on ECD cardiovascular involvement and its imaging assessment in the last decade are lacking.

Efficacy and safety of biological agents in adult-onset Still's disease.

OBJECTIVES: To describe the efficacy and safety of different biological agents in a large cohort of 20 patients with adult-onset Still's disease (AOSD). METHOD: We retrospectively evaluated 20 patients with severe or refractory AOSD treated with at least one biological agent (anakinra, etanercept, tocilizumab, and adalimumab), followed up for at least 12 months at our Institution. We collected and analysed data on the disease course, treatment outcome, and adverse effects, and compared our data with other published series. RESULTS: The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. In eight patients the biological agent that was first administered proved ineffective, and a switch to a different biologic was necessary. In three patients a third biologic was necessary to achieve disease control. The biologics eventually determined a clinical response in all patients. Patients with systemic disease showed better responses than patients with chronic articular disease (p < 0.05). Biological agents allowed either the withdrawal or the tapering of corticosteroid therapy (p < 0.0001) and of disease-modifying anti-rheumatic agents (DMARDs; p < 0.05). Three patients experienced herpes zoster reactivation. CONCLUSIONS: This is the longest follow-up of a cohort of AOSD patients treated with biological agents. Our data show that biologics are safe and generally effective in the long-term management of AOSD, particularly in cases with systemic disease, and suggest that a clinical response can be obtained in almost all AOSD patients, although a switch to drugs with a different mechanism of action may be necessary.

Inhibition of caspases maintains the antineoplastic function of gammadelta T cells repeatedly challenged with lymphoma cells.

T lymphocytes recognizing tumor antigens eventually undergo anergy or Fas-mediated death. V gamma9/V delta2+ T cells recognize poorly characterized ligand moieties on human B-cell lymphomas. Here we show that gammadelta T cells, a model for the study of activation-induced apoptosis, activate on repeated in vitro antigen-recognition caspase 3 and 8 and dramatically down-regulate their cytotoxic and secretory function. Caspase hindrance enhanced gammadelta T cell survival and sustained the killing of neoplastic cells and the release of IFN-gamma and tumor necrosis factor alpha. Caspases of tumor-specific T cells represent a candidate target to complement adoptive immunotherapy strategies.

Engagement of CD30 shapes the secretion of cytokines by human gamma delta T cells.

CD30 is a member of the TNF receptor superfamily, previously shown to be expressed on Hodgkin's lymphoma cells and on normal activated lymphocytes. We here show that CD30 is highly expressed on recently activated human gamma delta T cells. Elevated surface levels of this molecule persisted in long-term cultures of gamma delta cells, without further cell stimulation. CD30 acted as a co-stimulus in gamma delta T cells by potentiating the intracellular Ca(2+) fluxes induced by CD3 cross-linking. The engagement of CD30 enhanced the expression of several cytokines induced upon CD3 stimulation such as IL-4 and IFN-gamma but not IL-10. The CC chemokines RANTES and macrophage inflammatory protein-1beta were constitutively expressed and not affected by stimulation. The inducible expression of the neutrophil chemoattractant IL-8 was enhanced by CD30 co-stimulation, as well as that of the CC chemokines I-309 and MDC, whereas the secretion of the monocyte chemotactic protein-1 was not detected. Triggering of CD30 may therefore modulate the expression of several cytokines released by gamma delta cells; the expression of its physiologic ligand by APC and neutrophils at the site of infection may contribute to determine the outcome of an immune response.

[Use of calcium carbonate as an intestinal chelator of phosphorus]. / Utilizzo del calcio carbonato (CaCO3) come chelante intestinale del fosforo.

Fourteen patients undergoing periodic dialysis who had been taking AL(OH)3 as an intestinal chelant of phosphorus have been examined. AL(OH)3 was replaced by CaCO3 for a period of 6 months. At the end of the study, statistically significant reductions were evidenced in alkaline phosphatase, basal serum aluminiaemia and its increase after Desferal test, while the bicarbonates (HCO3) were found to be increased. Statistically non-significant increases were observed in calcaemia, PTH, and pH. It is concluded that the replacement of AL(OH)3 with CaCO3 is effective in controlling phosphoraemia, in diminishing serum concentrations and tissue deposits of Al and in improving uraemic acidosis.